Mucormycosis in COVID 19 times: Cases and their management from a unique perspective

The pathogen is ubiquitous, occurring naturally in the environment, the body surface, and orifices. The spores inoculate the paranasal sinuses and the nasopharynx with subsequent spread to the orbit and intracranial cavity in persons with decreased cellular and humoral defenses. The pathogen invades the vascular lamina propounding the inflammation with infarction and necrosis. Early diagnosis with the institution of appropriate antimicrobial therapy saves both sight and life. The present COVID‑19 pandemic has witnessed a resurgence of cases of rhino‑orbital mucormycosis.

A study documenting these cases and their management was done by Swati A Ravani and team published in Indian Journal of Ophthalmology.

The study is a retrospective, institutional cohort, interventional study. It was carried out at , B. J. Medical College, Ahmedabad, Institute of Ophthalmology from September 2020 to mid‑March 2021. All patients of biopsy‑proven mucormycosis were enrolled in the study. The patients were subjected to complete history taking, ophthalmological examination, and imaging studies. The patients were treated via a multidisciplinary approach with intravenous liposomal amphotericin B and debridement of local necrotic tissue. Exenteration was done when indicated.

Intravenous liposomal amphotericin B was given to all patients under the physician's guidance in a dose of 3 to 5 mg/kg body weight/day only after a confirmed microbiological or histopathological diagnosis of mucormycosis. The drug was not used empirically because of systemic side effects and high cost. The drug was continued until 4 to 7 days after resolution of the disease.

Oral posaconazole was added in a dose of 5 mg/kg body weight/day at the time of resolution. The combination therapy of liposomal amphotericin B and oral posaconazole was given for 4 to 7 days after resolution to allow for the onset of action of posaconazole.

Sinus debridement was done on the ENT side. Debridement of orbital necrotic tissue was done on ophthalmic side. Exenteration was considered in patients with the absence of light perception, total ophthalmoplegia, obvious necrosis of orbital tissues, and worsening despite the above concurrent systemic management.

The patient was subjected to serial imaging studies and/or nasal endoscopy to know the disease resolution or worsening. Repeat sinus and/or local tissue debridement was done on worsening. The resolution was evident on clinical improvement, hematology, and radiology. The resolution was confirmed by a negative sinus biopsy and normal metabolic parameters. Thereafter, the patient was discharged with continued medical management of comorbidities. Syrup posaconazole was continued orally after discharge for a minimum of 8 weeks as a protocol. The patients were followed up during the duration of the study, and the outcome was noted. A minimum follow-up period of 75 days was given to all patients.

In present study, most of the patients were in the fifth, sixth, and seventh decades of their life. The major risk factors included diabetes (96.7%) and COVID‑19 positivity (61.2%) with concurrent steroid use (61.2%). The duration from COVID‑19 positivity to presentation of mucormycosis was on an average of 2 months. The average value of HbA1c of diabetic patients was 7.57 mmol/mol.

The most common clinical presentation was diminution of vision (<6/60 in 80.64% of patients) and ophthalmoplegia (77.4%). The most common imaging findings were orbital cellulitis (61.29%) and pansinusitis (77.41%).

Intracranial extension in the form of cerebral involvement was seen in seven (22.58%) cases, internal carotid artery thrombosis in two (6.45%) cases, and cavernous sinus thrombosis in one (3.22%) case.

Intravenous liposomal amphotericin B was given to all patients. The average duration of intravenous amphotericin B was 18.93 days. Exenteration was required in four (12.9%) cases. Twenty‑eight patients (90.32%) recovered and were alive on the last follow‑up during the study period. Mortality occurred in three patients.

Presence of cerebral involvement and a HbA1c value of ≥8 were found to be significant in prediction of 75‑day mortality with a P value significance of ≤ 0.05. There were no recurrences during the follow-up period in the surviving patients.

Rhino‑orbital mucormycosis is an aggressive fungal opportunistic infection of the immune‑compromised, debilitated patients. The ubiquitous, naturally occurring fungus presents as a rhino‑orbital cerebral infection in those with weak innate immunity to fight the external invading pathogen. Classically, the clinical presentation has been described as an orbital cellulitis with proptosis, visual loss, and apical neuropathies.

An early diagnosis with a prompt, well‑coordinated, multidisciplinary approach has been vital to save both the life and sight of the patient. Microbiological diagnosis, control of the underlying systemic condition, and antimicrobial therapy with debridement of necrotic tissue have remained the mainstay of management of rhino‑orbital mucormycosis over the years. Exenteration may not be absolutely necessary if well managed.

The most common systemic risk factor was uncontrolled diabetes (96.7%).COVID‑19 positivity and concurrent steroid use further decreased the immunity in 61.2% of patients.

Although only 61.2% patients had a positive documented history of COVID‑19 infection in the recent past, the large cohort of rhino‑orbital mucormycosis seen is a far cry from the very few patients seen in pre‑COVID‑19 era. The average pre‑COVID‑19 era annual incidence of mucormycosis in the past 5 years (2015–2019) at our institute was 2.8 per year.

It has been well recognized in the clinical circles that the concurrent COVID‑19 infection with subsequent systemic steroid use in patients with immune‑compromised status as uncontrolled diabetes is the reason for the rise in mucormycosis cases.

There must be a high index of suspicion of rhino‑orbital mucormycosis in COVID‑19 era in all patients referred or presenting to the ophthalmologist with ophthalmoplegia and diminution of vision with or without history of concurrent uncontrolled diabetes mellitus. The numbers may represent just the tip of the iceberg. Rhino‑orbital cerebral mucormycosis and HbA1c ≥8 mmol/mol must be treated aggressively.

Source: Ravani SA, Agrawal GA, Leuva PA, Modi PH, Amin KD. Rise of the phoenix: Mucormycosis in COVID-19 times. Indian J Ophthalmol 2021;69:1563-8

DOI: 10.4103/ijo.IJO_310_21